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The incidence of sporadic early-onset colon cancer (EOCC) has increased worldwide. The molecular mechanisms in the tumor and the tumor microenvironment (TME) in EOCC are not fully understood. The aim of this study is to unravel unique spatial transcriptomic and proteomic profiles in tumor epithelial cells and cancer-associated fibroblasts (CAFs). Here, we divide the sporadic colon cancer tissue samples with transcriptomic data into patients diagnosed with EOCC (<50 yrs) and late-onset colon cancer (LOCC, ≥50 yrs) and then, analyze the data using CIBERSORTx deconvolution software. EOCC tumors are more enriched in CAFs with fibroblast associated protein positive expression (FAP(+)) than LOCC tumors. EOCC patients with higher FAP mRNA levels in CAFs have shorter OS (Log-rank test, p < 0.029). Spatial transcriptomic analysis of 112 areas of interest, using NanoString GeoMx digital spatial profiling, demonstrate that FAP(+) CAFs at the EOCC tumor invasive margin show a significant upregulation of WNT signaling and higher mRNA/protein levels of fibroblast growth factor 20 (FGF20). Tumor epithelial cells at tumor invasive margin of EOCC tumors neighboring FAP(+) CAFs show significantly higher mRNA/protein levels of fibroblast growth factor receptor (FGFR2) and PI3K/Akt signaling activation. NichNET analysis show a potential interaction between FGF20 and FGFFR2. The role of FGF20 in activating FGFR2/pFGFR2 and AKT/pAKT was validated in-vitro. In conclusion, we identify a unique FAP(+) CAF population that showed WNT signaling upregulation and increased FGF20 levels; while neighbor tumor cells show the upregulation/activation of FGFR2-PI3K/Akt signaling at the tumor invasive margin of EOCC tumors.
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Brain metastasis (BM) frequently occurs in patients with cutaneous melanoma, lung, and breast cancer; although, BM rarely arises from cancers of the gastrointestinal tract (GIT). The reported incidence of GIT cancer BM is less than 4%. In the last few years, effective systemic therapy has prolonged the survival of GIT patients and consequently, the incidence of developing BM is rising. Therefore, the epidemiology and biology of BM arising from GIT cancer requires a more comprehensive understanding. In spite of the development of new therapeutic agents for patients with metastatic GIT cancers, survival for patients with BM still remains poor, with a median survival after diagnosis of less than 4 months. Limited evidence suggests that early detection of isolated intra-cranial lesions will enable surgical resection plus systemic and/or radiation therapy, which may lead to an increase in overall survival. Novel diagnostic methods such as blood-based biomarker biopsies may play a crucial role in the early detection of BM. Circulating tumor cells and circulating cell-free nucleic acids are known to serve as blood biomarkers for early detection and treatment response monitoring of multiple cancers. Blood biopsy may improve early diagnosis and treatment monitoring of GIT cancers BM, thus prolonging patients' survivals.
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Neoplasias Encefálicas , Neoplasias Gastrointestinales , Melanoma , Neoplasias Cutáneas , Biomarcadores de Tumor , Biopsia , Neoplasias Encefálicas/secundario , Neoplasias Gastrointestinales/patología , HumanosRESUMEN
BACKGROUND: Recent studies have shown an association in non-metastatic colorectal cancer between patient survival and immunoprofiling (expression of CD3, CD4, CD8, CD45, and FOXP3 T cells at the invasive margin (IM) and the tumor center (TC)) regardless of stage. Patients with peritoneal carcinomatosis have a dismal prognosis, but survival can be significantly improved in selected patients who undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, current patient selection for CRS/HIPEC is suboptimal. The purpose of this study is to evaluate immune profiles of patients with peritoneal carcinomatosis and their correlation with overall survival (OS). METHODS: The study cohort included patients from a prospectively maintained database of adults with colorectal peritoneal carcinomatosis who underwent CRS/HIPEC. Immunohistochemistry (IHC) using antibodies to CD3, CD4, CD8, CD45RO, and FOXP3 T cells was performed. IHC image density was calculated using ImageJ software, and an immunoscore was determined. RESULTS: Eighty tumors were evaluated from 66 patients. These included 14 primary sites and 66 metastatic sites. R0/R1 resection was achieved in 44 (66.7%) patients. Known prognostic factors including resection status (HR 1.99, p = 0.004) and lymph node status (HR 3.49, p = 0.002) were associated with overall survival. On multivariate analysis, increased CD3/CD4 IM (HR 0.54, p = 0.03) ratio positively was associated with improved OS. DISCUSSION: This is the first study to assess the utility of subtypes of T cells as prognostic markers in patients with colorectal peritoneal carcinomatosis, which may play a role in patients with low-volume disease. Further studies into immune mechanisms may improve patient selection for cytoreductive surgery and HIPEC as well as provide novel pathways for effective immunotherapy.
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Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia del Cáncer por Perfusión Regional , Neoplasias Colorrectales/terapia , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Selección de Paciente , Neoplasias Peritoneales/terapia , PronósticoRESUMEN
BACKGROUND: Expression of CD3+ T cells, CD8+ cytotoxic T cells, CD45RO+ memory T cells, and FOXP3+ regulatory T cells at the invasive margin (IM) and tumor center (TC) has correlated with survival in gastric adenocarcinoma (GA) patients from East Asia, independent of anatomic staging. The reason for improved survival in East Asians compared with Western patients is a subject of debate. This study examined the immune profiles of a cohort of Western patients with GA, and their association with overall survival (OS). METHODS: Immunohistochemistry (IHC) using antibodies to CD3, CD4, CD8, CD45RO, and FOXP3 was performed on a randomly selected resected GA specimens from 88 Western patients. Cutoffs for high or low expression of each marker were determined with maximally selected rank statistics, and multivariable Cox proportional-hazards models constructed to evaluate the relationship between OS and expression of each marker at the IM and TC. RESULTS: Immune cell density was independent of anatomic staging. High expression of CD3, CD4, CD8, and CD45RO at the IM along with CD4 and FOXP3 at the TC were associated with improved OS. A combined marker of CD3, CD8, CD45RO, and FOXP3 associated with OS in East Asian GA was also validated. DISCUSSION: This is the first report in US patients to demonstrate that high expression of multiple subsets of T lymphocytes in GA is associated with better OS independent of clinical factors and anatomic stage. Further evaluation of immune-modulating mechanisms may explain survival differences between Western and Eastern patients and provide opportunity for novel treatments.
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Adenocarcinoma/inmunología , Adenocarcinoma/mortalidad , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/mortalidad , Adenocarcinoma/metabolismo , Adulto , Anciano , Antígenos de Diferenciación de Linfocitos T/metabolismo , Femenino , Humanos , Inmunohistoquímica , Antígenos Comunes de Leucocito/metabolismo , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias Gástricas/metabolismo , Linfocitos T , Microambiente TumoralRESUMEN
BACKGROUND: For patients with pancreatic adenocarcinoma (PA), the optimal time interval between neoadjuvant chemoradiation (CR) to surgical resection has not been well established. METHODS: The National Cancer Database from 2006 to 2014 was queried for patients ≥18 y old diagnosed with PA who received neoadjuvant CR. Survival and short-term outcomes were compared between patients who had pancreaticoduodenectomy ≤12 wk and >12 wk after completion of CR. RESULTS: 1610 patients met selection criteria. Average radiation to surgery (RS) interval was 58.2 ± 39.5 d. 1419 patients had RS interval ≤12 wk (mean 47.4 d) and 191 had RS interval >12 wk (mean 138.8 d). Demographics, CA 19-9 levels, types of chemotherapy and radiation dosage were similar between the two groups. There were more patients with clinical stage III cancers in the >12 wk group than in the ≤12 wk group (33.5% versus 14%). Short-term outcomes were similar between the two groups. However, a long-term survival benefit was observed in the >12 wk group (median 25.8 versus 30.2 mo P = 0.049). An interval >12 wk was associated with significantly prolonged survival on multivariate analysis (HR: 0.80, 95% CI: 0.65-0.99; P = 0.042). Higher clinical stage and positive surgical margins were independently associated with worse survival. CONCLUSIONS: Surgical resection beyond 12 wk after CR for PA did not worsen short-term outcomes. Waiting may contribute to better patient selection, especially those with locally advanced tumors. In the absence of progressive disease, patients need to be continuously evaluated for surgical resection after CR.
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Adenocarcinoma/terapia , Quimioradioterapia/métodos , Terapia Neoadyuvante/métodos , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomía/métodos , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Selección de Paciente , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Adequate lymph node (LN) sampling is critical for accurate nodal staging in colon cancer (CC), particularly for T3N0 disease as current guidelines recommend considering adjuvant chemotherapy when less than 12 LNs are examined. The impact of sidedness on nodal staging accuracy in patients with T3N0 disease has not been previously studied. METHODS: Patients with pathologic T3 CC were identified from a prospective multicenter international trial of ultrastaging in CC. The probability of true nodal negativity (TNN) based on the number of LN examined was calculated for right and left CC. These results were then validated in a cohort of patients with similar inclusion criteria selected from the National Cancer Database (NCDB) between 2006 and 2014. RESULTS: Three hundred and seventy patients met the inclusion criteria in the trial cohort; 48% were LN-negative. Of 153,945 patients in the NCDB, 57% were LN-negative. The probability of TNN when 12 LNs were examined was 68% for right and 64% for left CC in the trial cohort and 77% and 72% in the NCDB. The number of LNs needed to achieve any given probability of TNN was significantly different between right and left CC in both the trial (P<0.001) and the NCDB (P<0.001). CONCLUSIONS: In both a prospective multicenter trial and the NCDB, sidedness influences the number of LNs needed to predict nodal negativity in CC. Current guidelines regarding the minimum number of LNs needed to accurately stage patients with T3N0 CC may need to be re-evaluated by taking into consideration the tumor sidedness.
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BACKGROUND: Although resection historically played a prominent role in the treatment of metastatic melanoma, recent advances have altered the therapeutic landscape, and potentially the role of surgery. We examined surgical selection and metastasectomy outcomes before and after the onset of the effective drug therapy era. METHODS: Patients with stage IV melanoma were identified and characterized by treatment era (either 1965-2007 or 2008-2015) and by systemic therapy agents. BRAF and/or MEK inhibitors, as well as checkpoint inhibitors, were included as modern agents. Selection factors for metastasectomy were examined by era. A matched-pair analysis of outcomes of surgical and non-surgical patients receiving modern systemic agents was performed. RESULTS: Among 2353 eligible patients, 1065 (45.2%) underwent surgical treatment. Factors associated with selection for metastasectomy in the early era included female sex, no prior stage III disease, single-organ involvement, and M1a (vs. M1c) disease (all p < 0.007). In the current era, the proportion of surgically treated patients increased modestly (54.5% vs. 44.7%, p = 0.02) and age was the only independent selection factor (p < 0.01). Surgery followed by modern therapy in 47 matched pairs was associated with higher 5-year melanoma-specific survival (MSS) versus modern therapy alone (58.8% vs. 38.9%, p = 0.049). Multivariable regression showed single-organ involvement (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.21-0.90, p = 0.02) and first-line surgery (HR 0.47, 95% CI 0.23-0.98, p = 0.04), as well as use of modern agents (HR 0.29, 95% CI 0.21-0.40, p < 0.001), were independently associated with improved MSS. CONCLUSIONS AND RELEVANCE: While modern systemic agents have improved outcomes in stage IV melanoma, metastasectomy remains associated with favorable survival. Resection remains a viable therapeutic approach, possibly worthy of prospective evaluation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/mortalidad , Metastasectomía/mortalidad , Adulto , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Análisis por Apareamiento , Melanoma/tratamiento farmacológico , Melanoma/secundario , Melanoma/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaAsunto(s)
Neoplasias Colorrectales/patología , Reparación de la Incompatibilidad de ADN , Obesidad/complicaciones , Microambiente Tumoral/inmunología , Linfocitos T CD8-positivos/inmunología , Neoplasias Colorrectales/etiología , Factores de Transcripción Forkhead/metabolismo , Humanos , Obesidad/inmunología , Pronóstico , Linfocitos T Citotóxicos/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
BACKGROUND: Pancreatic surgery outcomes are associated with surgeon and center experience. Anesthesiologists as potential value drivers for pancreatic surgery have not been explored. We sought to evaluate whether anesthesiologists impact perioperative costs for pancreatic surgery. METHODS: Within an integrated health care system, 796 pancreatic surgeries (526 PDs and 270 DPs) were performed from January 2014 to June 2017. Mean direct operative and anesthesia costs driven by anesthesiologists (operating room (OR) time, anesthesia billing and anesthesia procedures) were determined for each case. The volumes of pancreatic cases per anesthesiologist were calculated, and those above the 75th percentile for volume (4 cases) were considered high-volume. A multivariable analysis of OR/anesthesia costs was performed. RESULTS: Mean OR and anesthesia costs for PD were $7064 for low-volume anesthesiologists (LVA), higher than $5968 for high-volume anesthesiologists (HVA) (p < 0.001). By multivariable analysis, HVA were associated with decreased costs of $2278 (p < 0.001). Teams of HVA and high-volume surgeons (HVS) were also associated with decreased mean costs of $1790 (p = 0.04). CONCLUSION: These data suggest that anesthesiologists experienced in the management of complex pancreatic operations such as PDs may contribute to improved efficiencies in care by reducing perioperative costs.
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Anestesiólogos , Ahorro de Costo , Pancreatectomía/economía , Pancreaticoduodenectomía/economía , Grupo de Atención al Paciente/organización & administración , Cirujanos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) being associated with a higher expression of CD8+ T cells. We hypothesized that a microbial signature might be associated with intratumoral immune cells as well as DFS. We found that the relative abundance of one Operational Taxonomic Unit (OTU), OTU_104, was significantly associated with recurrence even after applying false discovery correction (HR 1.21, CI 1.08 to 1.36). The final multivariable model showed that DFS was influenced by three parameters: N-stage, CD8+ labeling, as well as this OTU_104 belonging to the order Clostridiales. Not only were CD8+ labeling and OTU_104 significant contributors in the final DFS model, but they were also inversely correlated to each other (p=0.022). Interestingly, CD8+ was also significantly associated with the microbiota composition in the tumor: CD8+ T cells was inversely correlated with alpha diversity (p=0.027) and significantly associated with the beta diversity. This study is the first to demonstrate an association among the intratumoral microbiome, CD8+ T cells, and recurrence in CC. An increased relative abundance of a specific OTU_104 was inversely associated with CD8+ T cells and directly associated with CC recurrence. The link between this microbe, CD8+ T cells, and DFS has not been previously shown.
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BACKGROUND: Recent randomized trials suggest improved outcomes in patients with locally advanced colon cancer (LACC) treated with neoadjuvant chemotherapy (NAC). Optimal selection of patients for NAC depends on accurate clinical staging. The purpose of this study was to examine the degree of correlation between clinical and pathologic staging in patients with colon cancer (CC). METHODS: Adult patients with non-metastatic CC who underwent surgery were identified from the National Cancer Data Base between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging. RESULTS: One hundred five thousand five hundred sixty-nine patients were identified. The overall correlation rate between clinical and pathologic staging for T stage was 80% (kappa 0.7) and 83% for N stage (kappa 0.6). The correlation rate was 54% for T1, 76% for T2, 95% for T3, and 94% for T4 (P < 0.001). This compared with 81% for N0, 82% for N1, and 97% for N2 (P < 0.001). The sensitivity and specificity of clinical staging for identifying T3/T4 vs T1/T2 were 80 and 98%, respectively, compared to 60 and 98% for N1/N2 vs N0 (P < 0.001). CONCLUSIONS: Our findings suggest that current modalities used for clinical staging are accurate in predicting pathologic stage for advanced but not early T and N disease. Further optimization of clinical staging is essential for the accurate selection of patients who may benefit from neoadjuvant therapy and to avoid overtreatment of low-risk patients.
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Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Adulto , Anciano , Quimioterapia Adyuvante , Neoplasias del Colon/cirugía , Bases de Datos Factuales , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Sensibilidad y Especificidad , Carga TumoralRESUMEN
BACKGROUND: The association between tumor mismatch repair status and obesity in colon cancer is not well understood. The authors of this study hypothesized that mismatch repair deficiency in colon cancer may be associated with a lower Body Mass Index (BMI) and improved patient outcome due to an enhanced tumor immune microenvironment. METHODS: For this study, 70 patients were randomly selected from a prospective trial evaluating nodal ultrastaging for colon cancer. The mismatch repair status of tumors and immunomarker expression were correlated with clinicopathologic characteristics and evaluated for disease-free survival. RESULTS: Patients with mismatch repair-deficient tumors (n = 11) had a lower mean BMI than those with mismatch repair-proficient tumors (n = 59) (22.16 vs. 26.30 kg/m2, respectively; p = 0.029).The findings showed that CD3+ T cells were inversely associated with mismatch repair proficiency (p = 0.048). Mismatch repair-proficient tumors in nonobese patients (BMI < 30 kg/m2) versus obese patients had a higher density of CD8+ (p = 0.008) and FOXP3+ (p = 0.005) T cells. Multivariable analysis linked CD4+ (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.35-0.76), CD8+ (HR 0.67; 95% CI 0.50-0.89), and number of tumor-positive lymph nodes (HR 1.19; 95% CI 1.03-1.36) to disease-free survival for patients with mismatch repair-proficient tumors. CONCLUSIONS: Tumor mismatch repair status and obesity are correlated in patients with colon cancer. Increased intratumoral T cells in nonobese patients suggests an unexplored link between tumor mismatch repair and immunoprofile.
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Índice de Masa Corporal , Neoplasias del Colon/inmunología , Neoplasias del Colon/metabolismo , Reparación de la Incompatibilidad de ADN , Obesidad/inmunología , Microambiente Tumoral/inmunología , Anciano , Complejo CD3/metabolismo , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos/metabolismo , Proteínas de Unión al ADN/metabolismo , Supervivencia sin Enfermedad , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Metástasis Linfática , Recuento de Linfocitos , Masculino , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/metabolismo , Homólogo 1 de la Proteína MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Obesidad/genética , Estudios Prospectivos , Distribución AleatoriaRESUMEN
BACKGROUND: An initiative was established to improve value-based care for pancreatic surgery in a large nonprofit health system. Cost data were presented bimonthly to a hepatobiliary clinical performance group via videoconference. STUDY DESIGN: The direct costs were calculated for all patients undergoing distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) between January 2014 and July 2017. Median length of stay, 30-day and 90-day mortality rates, readmission rate, and costs were stratified by surgeon volume using 2 published criteria: "volume pledge" criteria (≥5 PDs/year) and Leapfrog criteria (≥11 PDs/year). RESULTS: There were 270 DPs and 526 PDs performed in 14 hospitals spanning 4 states. Median PD costs were lower for high-volume surgeons (≥5 PDs/year), $21,026 vs $24,706 (p = 0.005). High-volume surgeons had a shorter length of stay (9 days vs 11 days; p < 0.001) for PD and DP (6 days vs 7 days; p = 0.001). Increased costs for low-volume surgeons included operative/anesthesia costs ($7,321 vs $6,325; p = 0.03), room and board ($5,828 vs $4,580; p = 0.01), and intensive care costs ($4,464 vs $3,113; p = 0.04). Operating time was increased for high-volume surgeons for DP and PD (p < 0.001). There was no difference in 30-day or 90-day mortality rates or readmissions for DP or PD when stratified by volume pledge criteria. There was no difference in total costs for DP or PD when stratified by Leapfrog criteria. CONCLUSIONS: There was a significant cost reduction for PD but not DP when the threshold of 5 PDs was used as a definition of high volume. The sharing of detailed financial data with HPB surgeons on a regular basis provides an opportunity to evaluate practice patterns and thereby reduce direct costs.
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Prestación Integrada de Atención de Salud/economía , Pancreatectomía/economía , Pancreaticoduodenectomía/economía , Anciano , Costos y Análisis de Costo , Femenino , Hospitales de Alto Volumen , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pancreatectomía/mortalidad , Pancreaticoduodenectomía/mortalidad , Readmisión del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Estados UnidosRESUMEN
Accurate preoperative clinical staging is essential to optimize the treatment of rectal cancer. Primary surgical resection is typically indicated for stage I disease, whereas neoadjuvant therapy is recommended for stages II and III. The objective of this study is to examine the accuracy of clinical staging using current imaging modalities in predicting pathologic stage and, thus, selecting appropriate treatment. Adult patients with nonmetastatic rectal cancer who underwent primary surgical resection were identified from the National Cancer Database between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging. A total of 13,175 patients were identified. The correlation between clinical and pathologic staging was 69 per cent for stage I (31% upstaged) (Kappa 0.54, P < 0.001). One-third of patients who were clinically staged as stage I, and were therefore treated with primary surgical resection, had pathologic stage II or III disease. Based on their clinical staging, those patients did not receive the neoadjuvant therapy recommended by present guidelines. Where accurate clinical staging is in doubt, oncologists should carefully examine the quality of staging modality and perhaps consider multimodal imaging using both endorectal ultrasound and MRI.
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Adenocarcinoma/cirugía , Neoplasias del Recto/cirugía , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Estadificación de Neoplasias , Selección de Paciente , Cuidados Preoperatorios/métodos , Neoplasias del Recto/epidemiología , Neoplasias del Recto/patología , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: In 2016, the National Comprehensive Cancer Network included neoadjuvant chemotherapy as a treatment option for patients with clinical T4b colon cancer. However, there is little published data on the survival impact of neoadjuvant chemotherapy for locally advanced colon cancer. METHODS: Adult patients with non-metastatic clinically staged T3 or T4 colon cancer who underwent surgical resection were identified from the National Cancer Data Base between 2006 and 2014. Treatment was categorized as neoadjuvant chemotherapy followed by surgery and surgery followed by adjuvant chemotherapy. Overall survival was compared between the two groups using propensity score matching. RESULTS: Of 27,575 patients that met inclusion criteria, 26,654 (97%) were treated with surgery followed by adjuvant chemotherapy and 921 (3%) received neoadjuvant chemotherapy followed by surgery. After propensity score matching, patients with T4b colon cancer treated with neoadjuvant chemotherapy had a 23% lower risk of death at 3 years compared to patients that had adjuvant chemotherapy (HR 0.77, 95% CI 0.60-0.98; p = 0.04). However, neoadjuvant chemotherapy did not demonstrate a similar significant benefit for patients with T3 and T4a disease. CONCLUSIONS: Patients with clinical T4b colon cancer treated with neoadjuvant chemotherapy may have an improved survival compared to those who receive adjuvant chemotherapy. Further prospective investigation is warranted.
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Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/cirugía , Adulto , Anciano , Quimioterapia Adyuvante , Neoplasias del Colon/patología , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Periodo Posoperatorio , Periodo Preoperatorio , Puntaje de Propensión , Tasa de SupervivenciaRESUMEN
Importance: Systemic therapy for metastatic melanoma has evolved rapidly during the last decade, and patient treatment has become more complex. Objective: To evaluate the survival benefit achieved through surgical resection of melanoma metastatic to the abdominal viscera in patients treated in the modern treatment environment. Design, Setting, and Participants: This retrospective review of the institutional melanoma database from the John Wayne Cancer Institute at Providence St Johns Health Center, a tertiary-level melanoma referral center, included 1623 patients with melanoma diagnosed as having potentially resectable abdominal metastases before (1969-2003) and after (2004-2014) advances in systemic therapy. Main Outcomes and Measures: Overall survival (OS). Results: Of the 1623 patients identified in the database with abdominal melanoma metastases, 1097 were men (67.6%), and the mean (SD) age was 54.6 (14.6) years. Of the patients with metastatic melanoma, 1623 (320 [19.7%] in the 2004-2014 period) had abdominal metastases, including 336 (20.7%) with metastases in the gastrointestinal tract, 697 (42.9%) in the liver, 138 (8.5%) in the adrenal glands, 38 (2.3%) in the pancreas, 109 (6.7%) in the spleen, and 305 (18.8%) with multiple sites. Median OS was superior in surgical (n = 392; 18.0 months) vs nonsurgical (n = 1231; 7.0 months) patients (P < .001). The most favorable 1-year and 2-year OS was seen after surgery for gastrointestinal tract (52% and 41%) and liver (51% and 38%) metastases, respectively. Multivariable analysis found increasing age (hazard ratio [HR], 1.01; 95% CI, 1.00-1.01; P = .02) and the presence of ulceration (HR, 1.21; 95% CI, 1.01-1.45; P = .04) were associated with a worse OS. Alternatively, treatment with metastasectomy (HR, 0.59; 95% CI, 0.46-0.74; P < .001) and metastases involving the gastrointestinal tract (HR, 0.65; 95% CI, 0.48-0.87; P = .004) were associated with a better OS. The systemic treatment era did not significantly affect outcomes (HR, 0.82; 95% CI, 0.67-1.02; P = .15). Overall, patients with gastrointestinal tract metastases undergoing complete, curative resection derived the greatest benefit, with a median OS of 64 months. Conclusions and Relevance: To our knowledge, this series is the largest single-institution experience with abdominal melanoma metastases, demonstrating that surgical resection remains an important treatment consideration even in the systemic treatment era.
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Neoplasias de las Glándulas Suprarrenales/cirugía , Neoplasias del Sistema Digestivo/cirugía , Neoplasias Gastrointestinales/cirugía , Neoplasias Hepáticas/cirugía , Melanoma/cirugía , Neoplasias Pancreáticas/cirugía , Neoplasias del Bazo/cirugía , Neoplasias de las Glándulas Suprarrenales/tratamiento farmacológico , Neoplasias de las Glándulas Suprarrenales/secundario , Adulto , Factores de Edad , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias del Sistema Digestivo/tratamiento farmacológico , Neoplasias del Sistema Digestivo/secundario , Femenino , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/secundario , Humanos , Ipilimumab , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Melanoma/tratamiento farmacológico , Melanoma/secundario , Metastasectomía , Persona de Mediana Edad , Nivolumab , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/secundario , Estudios Retrospectivos , Neoplasias del Bazo/tratamiento farmacológico , Neoplasias del Bazo/secundario , Tasa de SupervivenciaRESUMEN
BACKGROUND: There is no consensus on the relationship between patient sex and the location, stage, and oncologic outcome of colon cancer (CC). We hypothesized that there is a sex-specific difference in the biology and management of CC. STUDY DESIGN: Our cohort was drawn from a database of patients enrolled in international trials of nodal ultrastaging for nonmetastatic CC. These trials required strict adherence to surgical and pathologic quality measures. Postoperative follow-up included colonoscopy at 1 and 4 years and annual CT scans. Sex-specific differences in tumor biology, location, stage, and recurrence were evaluated by chi-square, Fischer's exact, and independent t-tests. RESULTS: The cohort included 435 males (median age 69 years) and 423 females (median age 70 years). Females had more right-sided (p = 0.03) and earlier T stage (p = 0.05) tumors, but there was no sex-based difference in pathologic grade, total lymph nodes retrieved, nodal positivity (p = 0.47) or lymphovascular invasion (p = 0.45). The overall 4-year disease-free survival (DFS) was comparable in females and males (77.9% and 77.5%, respectively). By multivariate analysis, only nodal positivity and cancer recurrence affected overall survival (OS) (p = 0.008). Neither sex nor primary tumor affected DFS or OS. CONCLUSIONS: This is the first prospective study to demonstrate sex-specific differences in location and T stage of CC when surgical and pathologic management adhered to strict quality standards. The predominance of right-sided CC in females suggests that flexible sigmoidoscopy may be inadequate for screening and surveillance. Interestingly, earlier stage and right-sided location did not confer a DFS or OS advantage for women. Additional studies are needed to determine why females have a higher propensity for right-sided lesions and a potential difference in CC biology.
Asunto(s)
Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Metástasis Linfática/patología , Anciano , Neoplasias del Colon/epidemiología , Colonoscopía , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Estudios Prospectivos , Garantía de la Calidad de Atención de Salud , Factores Sexuales , Tasa de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. HYPOTHESIS: Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. DESIGN: This study was designed as single-blinded PRCT. SETTING: This study was conducted in an academic medical center. PATIENTS AND METHODS: Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0-10). RESULTS: Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p < 0.001) at all early (1-6 h) post-operative time points following LC. CONCLUSION: This PRCT shows significantly improved pain control with somatovisceral pain blockade over non-opioid/opioid analgesic combinations following LC for symptomatic cholelithiasis. For centers not utilizing adjunctive local anesthetic for LC, this topical use of bupivacaine may improve patient comfort during recovery. This trial was registered on www.ClinicalTrials.gov NCT# 01972620.